期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 431, 期 17, 页码 3146-3156出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2019.06.012
关键词
ubiquitin; UBAN; phosphorylation; ABIN-1; OPTN
资金
- DFG [SFB 1177]
- Cluster of Excellence Macromolecular Complexes of the Goethe University Frankfurt [EXC 115]
- LOEWE grant Ub-Net
- LOEWE Centrum for Gene and Cell Therapy Frankfurt
- European Molecular Biology Organization long-term postdoctoral fellowship
Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of UBAN/di-Ub binding stoichiometry. Analysis of UBAN/M1-linked di-Ub binding characteristics indicates that phosphorylated S473 in OPTN and its corresponding phospho-mimetic residue in ABIN-1 (E484) are essential for high affinity interactions with M1-linked Ub chains. Also, a phospho-mimetic mutation of A303 in NEMO, corresponding to S473 of OPTN, increases binding affinity for M1-linked Ub chains. These findings are in line with the diverse physiological roles of UBAN domains, as phosphorylation of OPTN UBAN is required to enhance its binding to Ub during mitophagy. (C) 2019 Elsevier Ltd. All rights reserved.
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